The cGAS–STING pathway drives type I IFN immunopathology in COVID-19

Abstract COVID-19, which is caused by infection with SARS-CoV-2, is characterized by lung pathology and extrapulmonary complications 1,2 . Type I interferons (IFNs) have an essential role in the pathogenesis of COVID-19 (refs 3–5 ). Although rapid induction of type I IFNs limits virus propagation, a sustained increase in the levels of type I IFNs in the late phase of the infection is associated with aberrant inflammation and poor clinical outcome 5–17 . Here we show that the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, which controls immunity to cytosolic DNA, is a critical driver of aberrant type I IFN responses in COVID-19 (ref. 18 ). Profiling COVID-19 skin manifestations,…

• NF
  Novartis Foundation
• FA
  Fondation Acteria
• EC
  European Commission

  Awards: COVID-19, 804933
• NS
  Novartis Stiftung für Medizinisch-Biologische Forschung
• FL
  Fondation Leenaards
• UD
  Université de Lausanne
• CH
  Centre Hospitalier Universitaire Vaudois
• HE
  H2020 European Research Council